Neoadjuvant chemoimmunotherapy confers survival advantage for patients undergoing sleeve lobectomy.

OBJECTIVES: It has been demonstrated that neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy was safe and feasible referred to neoadjuvant chemotherapy for patients with non-small cell lung cancer undergoing sleeve lobectomy. Nevertheless, no survival data were reported in the previous researches. Therefore, we conducted this study to compare neoadjuvant ICI plus chemotherapy versus neoadjuvant chemotherapy followed by sleeve lobectomy for long-term survival outcomes. METHODS: Patients who underwent bronchial sleeve lobectomy following neoadjuvant ICI plus chemotherapy or neoadjuvant chemotherapy were retrospectively identified. Treatment response, perioperative outcomes, event-free survival and overall survival were compared between groups in the overall and the inverse probability of treatment weighting-adjusted cohort. RESULTS: A total of 139 patients with 39 lung cancer recurrence and 21 death were included. Among them, 83 (59.7%) and 56 (40.3%) patients received neoadjuvant chemotherapy and neoadjuvant ICI plus chemotherapy, respectively. After inverse probability of treatment weighting, more patients achieved complete pathological response in the neoadjuvant ICI plus chemotherapy group (6.0% vs 26.3%, P < 0.001). There was no significant difference regarding overall postoperative complication (23.8% vs 20.2%, P = 0.624) and specific complications (all P > 0.05). Patients receiving neoadjuvant ICI plus chemotherapy had favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.16-0.85, P = 0.020) and overall survival (hazard ratio 0.23, 95% confidence interval 0.06-0.80, P = 0.021). Multivariable analysis revealed that neoadjuvant ICI plus chemotherapy was an independent predictor for favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.15-0.86, P = 0.020, adjusted for clinical TNM stage). CONCLUSIONS: Neoadjuvant ICI plus chemotherapy was correlated with favourable long-term survival in patients with non-small cell lung cancer undergoing sleeve lobectomy.

Prognostic outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical epidermal growth factor receptor mutations.

OBJECTIVES: Limited data exist on the characteristics of atypical epidermal growth factor receptor (EGFR) mutations in early-stage lung cancer. Our goal was to elucidate the associations with outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical EGFR mutations. METHODS: Eligible patients between 2014 and 2019 were retrospectively identified and grouped into exon20 insertion mutations and major atypical mutations, which included G719X, L861Q and S768I. Disease-free survival (DFS) was evaluated in the entire cohort and stratified by radiologic characteristics. Recurrence patterns were investigated and compared between groups. A competing risk model was used to estimate the cumulative incidence of recurrence. RESULTS: A total of 710 patients were finally included. Among them, 289 (40.7%) patients had exon 20 insertion mutations and 421 (59.3%) patients had major atypical mutations. There was no significant difference regarding DFS (P = 0.142) between groups in the entire cohort. The interaction between mutation subtype and the presence of ground-glass opacities was significant (hazard ratio 2.00, 95% confidence interval 1.59-2.51, P < 0.001), indicating DFS between exon 20 insertion mutations and major atypical mutations may be different among subsolid and solid tumours. Survival analysis consistently revealed no significant difference in subsolid tumours (P = 0.680), but favourable DFS of exon 20 insertion mutations in solid tumours (P = 0.037). Furthermore, patients with exon 20 insertion mutations had a lower risk of developing bone metastases did those with radiologic solid tumours (Gray's test, P = 0.012). CONCLUSIONS: Exon 20 insertion mutations were correlated with favourable DFS and lower incidence of bone metastases in radiologic solid lung adenocarcinomas harbouring atypical EGFR mutations.

Prognostic Significance of the Proposed Residual Tumor Classification in Patients With NSCLC After Sleeve Lobectomy.

Introduction: To validate the residual tumor (R) classification proposed by the International Association for the Study of Lung Cancer (IASLC) in NSCLC after sleeve lobectomy. Methods: A total of 682 patients were analyzed. The R status, on the basis of the Union for International Cancer Control (UICC) criteria, was recategorized according to the IASLC descriptors. Recurrence-free survival (RFS) and overall survival (OS) among different R classifications were assessed for the entire cohort and pathologic node (pN) subgroups. Results: All in all, 631 (92.5%), 48 (7.1%), and three patients (0.4%) were classified as R0, R1, and R2, respectively, by the UICC criteria, whereas 489 (71.7%), 110 (16.1%), and 83 patients (12.2%), received R0, uncertain resection (R[un]), and R1/2 resection, respectively, according to the IASLC criteria. There were 96 patients (15.2%) with UICC R0 who were reclassified as R(un), mainly because of the positive highest mediastinal node station (82 of 96, 85.4%). A total of 46 patients (7.3%) were reassigned from UICC R0 to IASLC R1/2 owing to extracapsular extension. For the entire cohort, patients with R(un) and R1/2 exhibited worse RFS (R[un], adjusted p = 0.023; R1/2, adjusted p = 0.001) and OS (R[un], adjusted p = 0.040; R1/2, adjusted p = 0.051) compared with R0. No significant differences were observed between R(un) and R1/2 (RFS, adjusted p = 0.586; OS, adjusted p = 0.781). Furthermore, subgroup analysis revealed a distinct prognostic impact of the IASLC R status-with prognostic significances in the pN1 and pN2 subgroups, but not in the pN0 subgroup. Conclusions: The IASLC R descriptors helped to stratify the prognosis of NSCLC after sleeve lobectomy, with its prognostic impact varied among pN stages.

P110α inhibitor alpelisib exhibits a synergistic effect with pyrotinib and reverses pyrotinib resistant in HER2+ breast cancer.

Human epidermal growth factor receptor 2 (HER2) plays a critical role in breast cancer progression in patients with HER2 overexpression, thereby driving the development of targeted drugs and advancing therapy strategies targeting this gene. Pyrotinib is a novel irreversible pan-ErbB kinase inhibitor, primarily suppresses the downstream MAPK and PI3K/AKT pathways. Alpelisib, a selective PI3K p110α inhibitor, has been approved for clinical application in HR+, HER2-, PIK3CA mutated breast cancers and is also being developed for use in other breast cancer subtypes. In this study, we hypothesised that combining pyrotinib with alpelisib would yield superior results compared to single-drug treatment. Our data demonstrated that the combination of alpelisib and pyrotinib exhibited a synergistic effect in HER2+ breast cancer both in vitro and in vivo. This combination led to decreased cell proliferation and migration, G0-G1 cell cycle arrest, and increased apoptosis rates. Additionally, the deactivation of ErbB receptors and sustained activation of PI3K/AKT pathway by upstream compensatory pathways induced acquired pyrotinib resistant cells resistant to pyrotinib treatment, thus alpelisib combined with pyrotinib showed a tremendous synergistic effect and reverse pyrotinib resistance in acquired pyrotinib resistant cells by suppressing the activated PI3K/AKT pathway. Our results revealed a combination of pyrotinib and alpelisib as an effective therapeutic strategy in treating HER2+ breast cancer, whether sensitive or resistant to pyrotinib treatment.

LINC00891 promotes tumorigenesis and metastasis of thyroid cancer by regulating SMAD2/3 via EZH2.

BACKGROUND: Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays. METHODS: To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. In vitro experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion apoptosis, and of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting. RESULTS: Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown. CONCLUSION: In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment.

PDZK1IP1 gene promotes proliferation, migration, and invasion in papillary thyroid carcinoma.

Thyroid cancer is a common malignant tumor for the adult and the potential molecular mechanism of papillary thyroid cancer cell metastasis is still unclear. We used sequencing techniques to analyze paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissue and identified a gene, PDZK1IP1, that was significantly overexpressed in thyroid cancer. We found It has been detected to play an important role in many malignant tumors. But the role in papillary thyroid cancer was still unknown, we decided to find a new marker and therapeutic target for the disease. The present study shows that PDZK1IP1 may be a potential gene that leads to thyroid cancer. In our study, silencing PDZK1IP1 can inhibit PTC cell proliferation, migration, invasion, apoptosis, and cell cycle arrest. This study surmised that PDZK1IP1 was an oncogene that correlated with tumor development.

AHNAK2 promotes the progression of differentiated thyroid cancer through PI3K/AKT signaling pathway.

AIMS: AHNAK2 may be used as a candidate marker for TC diagnosis and treatment. BACKGROUND: Thyroid cancer [TC] is the most frequent malignancy in endocrine carcinoma, and the incidence has been increasing for decades. OBJECTIVE: To understand the molecular mechanism of DTC, we performed next-generation sequencing [NGS] on 79 paired DTC tissues and normal thyroid tissues. The RNA-sequencing [RNA-seq] data analysis results indicated that AHNAK nucleoprotein 2 [AHNAK2] was significantly upregulated in the thyroid cancer patient's tissue. METHOD: We also analyzed AHNAK2 mRNA levels of DTC tissues and normal tissues from The Cancer Genome Atlas [TCGA]. The association between the expression level of AHNAK2 and clinicopathological features was evaluated in the TCGA cohort. Furthermore, AHNAK2 gene expression was analyzed by quantitative real-time polymerase chain reaction [qRT-PCR] in 40 paired DTC tissues and adjacent normal thyroid tissues. The receiver operating characteristic [ROC] curve was performed to evaluate the diagnostic value of AHNAK2. For cell experiments in vitro, AHNAK2 was knocked down using small interfering RNA [siRNA], and the biological function of AHNAK2 in TC cell lines was investigated. The expression of AHNAK2 was significantly upregulated in both the TCGA cohort and the local cohort. RESULT: The analysis results of the TCGA cohort indicated that the upregulation of AHNAK2 was associated with tumor size [P<0.001], lymph node metastasis [P<0.001], and disease stage [P<0.001]. The area under the curve [AUC] [TCGA: P<0.0001; local validated cohort: P<0.0001.] in the ROC curve revealed that AHNAK2 might be considered a diagnostic biomarker for TC. The knockdown of AHNAK2 reduced TC cell proliferation, colony formation, migration, invasion, cell cycle, and induced cell apoptosis. CONCLUSION: Furthermore, the protein levels of phospho-PI3 Kinase p85 and phospho-AKT were down-regulated in the transfected TC cell. Our study results indicate that AHNAK2 may promote metastasis and proliferation of thyroid cancer through PI3K/AKT signaling pathway. Thus, AHNAK2 may be used as a candidate marker for TC diagnosis and treatment.

Glucose-to-Lymphocyte Ratio (GLR) as a Predictor of Preoperative Central Lymph Node Metastasis in Papillary Thyroid Cancer Patients With Type 2 Diabetes Mellitus and Construction of the Nomogram.

Background: Detection of metastasis of central lymph nodes in papillary thyroid cancer is difficult before surgery. The role of routine or preventive central lymph node dissection in the management of papillary thyroid cancer remains inconclusive. Moreover, glucose metabolism and systemic inflammation are related to the aggressiveness of several malignant tumors and the prognoses of these patients. This study aimed to construct a nomogram based on the readily available preoperative clinical features for predicting the occurrence of preoperative central lymph node metastasis in patients with papillary thyroid cancer and type 2 diabetes mellitus. The findings may underlie clinical implications for determining the appropriate treatment strategies for these patients. Methods: A total of 419 patients were enrolled. We used the receiver operating characteristic curves to determine the best cut-off value and converted the continuous into categorical variables. Next, a single-factor logistic analysis for the independent variables was performed, following which a multivariate regression analysis was conducted for the selected significant risk factors. Finally, the nomogram was constructed and verified using external data; the existing data were compared with the original model. Results: According to the receiver operating characteristic curves, the best cut-off values ​​for glucose-to-lymphocyte ratio and tumor size were 4.23 cm and 0.95 cm, respectively. Findings from the multivariate logistic regression analysis suggested that age, bilateral tumors, maximum tumor size, and the ratio of glucose-to-lymphocytes were independent risk factors for preoperative central lymph node metastasis. The C-indexes in the training and the external validation data sets were 0.733 and 0.664, respectively. Both calibration curves and the Hosmer-Lemeshow tests indicated that the model was well-calibrated. Through decision curve analysis, the predictive model was estimated to have strong clinical applicability and greater benefits. To compare the performance of the new with that of the original model, we performed a net reclassification index and the integrated discrimination improvement analyses, both of which indicated that the new model had a better predictive ability. Conclusion: In patients with type 2 diabetes mellitus and papillary thyroid cancer, a high preoperative glucose-to-lymphocyte ratio was an independent predictor of the preoperative central lymph node metastasis. The nomogram so constructed could better predict the preoperative central lymph node metastasis in these patients.

The ETNK2 gene promotes progression of papillary thyroid carcinoma through the HIPPO pathway.

Thyroid cancer is a disease with an extremely high incidence rate and is divided into papillary, follicular, medullary, and undifferentiated thyroid cancers. Among them, papillary carcinoma is the most common subtype. We assessed expression of ETNK2 in public databases and found that ETNK2 is upregulated in PTC. Cohort and RNA sequencing data were used to verify this discovery. To further determine the relationship between ETNK2 and papillary thyroid carcinoma, we performed an in vitro experiment. In a PTC cell line, silencing ETNK2 inhibited cell proliferation, weakened cell migration and invasion ability, promoted apoptosis, and blocked the cell cycle. In addition, western blotting suggested that ETNK2 is related to the HIPPO pathway and may activate the EMT pathway through the HIPPO pathway to promote the development of thyroid cancer. These results revealed that ETNK2 is related to the occurrence and development of papillary thyroid carcinoma, suggesting that ETNK2 may be an oncogene associated with PTC.

SYT12 is a novel oncogene that promotes thyroid carcinoma progression and metastasis.

Background: Thyroid malignancy is the most frequent endocrine malignant tumor whose incidence is still increasing. Mechanisms genomic variations play a major part in the pathogenesis of many types of malignancy. Synaptotagmin 12 (SYT12) is a member gene of the synaptotagmins family and SYT12's variants were shown to be associated with some malignancies. Nevertheless, SYT12's specific function and probable clinical value in papillary cancer were still unknown. Methods: We conducted complete genome sequence of 39 pairs PTC malignant neoplasm and matched non-neoplastic tissues. We found that SYT12 was significantly overexpressed in thyroid malignancy. Next, we investigated the expression level of SYT12 and the relation between clinical information and SYT12 expression in thyroid cancer in the Cancer Genome Atlas (TCGA). QRt-PCR of else 40 pairs local verified cohort was performed to confirm the sequencing data and TCGA cohort. Then, we used small interfering RNA (si-RNA) to knock down the expression of SYT12 in PTC cells. Finally, proliferation, cell colony formation, migration, invasion, and apoptosis assays were done to demonstrate the function of SYT12. Results: SYT12 is significantly overexpressed and higher expression of SYT12 upsurges the risk of lymph node metastatic and incidence rate of primary neoplasm multivariate focus type and classical histological type for PTC patients in TCGA cohort. In vitro experiments, the results of functional assays presented that knock-down of SYT12 inhibited the cell proliferation, cell colony formation, trans-well migration, and trans-well invasion and promoted cell apoptotic in PTC cell lines. Conclusion: SYT12 was a novel oncogene that promotes thyroid carcinoma progression and metastasis potential and a potential biomarker for diagnosis and treatment in PTC.

Pan-cancer analysis of the prognostic and immunological role of PSMB8.

Recently some evidence has demonstrated the significance of PSMB8 in various malignancies. Nevertheless, PSMB8 (proteasome subunit beta 8), more familiar in the field of immunology contributing to the process of antigen presentation, is indeterminate in the role as a survival predictor of human pan-cancer. Besides, how PSMB8 interacts with immune cell infiltration in the tumor microenvironment requires further research. We then penetrated into the analysis of the PSMB8 expression profile among 33 types of cancer in the TCGA database. The results show that overexpression of PSMB8 was associated with poor clinical outcomes in overall survival (Sartorius et al. in Oncogene 35(22):2881-2892, 2016), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in most cancer varieties. In addition, there existed distinctly positive correlations between PSMB8 and immunity, reflected straightforwardly in the form of immune scores, tumor-infiltrating immune cells (TIICs) abundance, microsatellite instability, tumor mutation burden, and neoantigen level. Notably, specific markers of dendrite cells exhibited the tightest association with PSMB8 expression in terms of tumor-related immune infiltration patterns. Moreover, gene enrichment analysis showed that elevated PSMB8 expression was related to multiple immune-related pathways. We finally validated the PSMB8 expression in our local breast samples via quantitative PCR assays and concluded that PSMB8 appeared to perform well in predicting the survival outcome of BRCA patients. These findings elucidate the pivotal role of the antigen presentation-related gene PSMB8, which could potentially serve as a robust biomarker for prognosis determination in multiple cancers.

PSD3 is an oncogene that promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in papillary thyroid cancer.

Background: The morbidity of thyroid cancer is gradually increasing, meanwhile, the average age of the morbidity population also becomes younger. Mechanisms genomic variations serve an important function for the pathogenesis of many cancer types. Pleckstrin and sec7 domain-containing 3 (PSD3), also known as EFA6R, was shown to be associated with some cancers such as acute myeloid leukemia, breast cancer metastasis, and astrocytoma. But it was unknown that whether PSD3 took effect and how did it work in thyroid cancer. Methods: We guessed that PSD3 might play an important role in thyroid cancer by consulting previous literature. Then, we analyzed the level of PSD3 expression in thyroid malignancy and the connection with clinical manifestation in The Cancer Genome Atlas (TCGA). And RNA extraction, reverse transcription, and real-time quantitative polymerase chain reaction (qRt-PCR) of 40 pairs of local samples were done to verify the result of TCGA. Then, PSD3 was knocked down by small interfering RNA (siRNA) for flowing functional experiments. Results: Bioinformatics and qRt-PCR analysis shown PSD3 was overexpressed in papillary thyroid cancer (PTC) and connected with the histological type (P=0.009) and risk of lymph node metastasis (P=0.016). In vitro assays, we confirmed that down-regulation PSD3 could not only suppress the cell proliferation, colony formation, cell migration, cell invasion, and G1/S cell cycle transition but also promote apoptosis in PTC cells. Conclusion: PSD3 promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in PTC and a possible biomarker in PTC.

LEM domain containing 1 promotes thyroid cancer cell proliferation and migration by activating the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition.

Thyroid cancer (TC) is the most common type of endocrine malignancy in humans, and its relative incidence has increased continuously in recent years. However, the primary molecular mechanisms of thyroid tumorigenesis and progression remain unclear. Papillary TC (PTC) is the most common subtype of TC. Recent studies have reported that one of the tumorigenesis and progression mechanisms is driven by genetic alterations that regulate the TC cell signaling pathway. In the present study, RNA sequencing (RNA-seq) was performed on 79 paired PTC and adjacent normal thyroid tissues to further study the molecular mechanisms of TC. Reverse transcription-quantitative PCR was used to detect the expression levels of LEM domain containing 1 (LEMD1) in 47 paired PTC and adjacent normal thyroid tissue samples. Initial analysis revealed that LEMD1 expression was significantly upregulated in TC tissues compared with that in normal tissues. The results of the thyroid RNA-seq datasets from The Cancer Genome Atlas were consistent with the RNA-seq analysis results of the present study. High LEMD1 expression increased the risk of lymph node metastasis in patients with TC. The biological function of LEMD1 on cell proliferation, migration, invasion and apoptosis was investigated in vitro via small interfering RNA and overexpression vector. Gene set enrichment analysis indicated that high LEMD1 expression was associated with epithelial-mesenchymal transition (EMT) and the Wnt/ß-catenin signaling pathway. Western blotting revealed that LEMD1 modulated the protein expression levels of E-cadherin, N-cadherin, vimentin, ß-catenin and cleaved-caspase 3. In conclusion, the present results indicated that LEMD1 may drive TC cell tumorigenesis and progression by activating the Wnt/ß-catenin signaling pathway and EMT.

Genetic landscape of breast cancer and mutation tracking with circulating tumor DNA in Chinese women.

Considerable efforts have been devoted to exploring the breast cancer mutational landscape to understand its genetic complexity. However, no studies have yet comprehensively elucidated the molecular characterization of breast tumors in Chinese women. This study aimed to determine the potential clinical utility of peripheral blood assessment for circulating tumor-derived DNA (ctDNA) and comprehensively characterize the female Chinese population's genetic mutational spectrum. We used Omi-Seq to create cancer profiles of 273 patients enrolled at The First Affiliated Hospital of Wenzhou Medical University. The gene landscape results indicate PIK3CA and TP53 as the most frequently detected genes, followed by ERBB2, in Chinese breast cancer patients. The accuracy of ERBB2 copy number variations in tissue/formalin-fixed and paraffin-embedded samples was 95% with 86% sensitivity and 99% specificity. Moreover, mutation numbers varied between different molecular cell-free DNA subtypes, with the basal-like patients harboring a higher number of variants than the luminal patients. Furthermore, ratio changes in the max ctDNA allele fraction highly correlated with clinical response measurements, including cancer relapse and metastasis. Our data demonstrate that ctDNA characterization using the Omi-Seq platform can extend the capacity of personalized clinical cancer management.

Stress-induced phosphoprotein 1 facilitates breast cancer cell progression and indicates poor prognosis for breast cancer patients.

Breast cancer (BC) threatened the life health of a tremendous amount of the population, and the estimated number of death is still rising nowadays. We found that stress-induced phosphoprotein 1 (STIP1) is overexpressed in BC tissues compared to non-tumorous breast tissues. Our study is to validate the prognostic value of STIP1 and investigate its biological role in BC. We verified the upregulation of STIP1 in multiple databases, proved that STIP1 is upregulated in BC tissues and cell lines using real-time quantitative PCR (qRT-PCR). We used small interfering RNA to examine the function of STIP1 in BC cell lines (BT-549, MDA-MB-231, Hs-578 T) and explored the mechanism of function of STIP1 in BC cells using Western blotting and qRT-PCR. Analyses of multiple databases indicated that high STIP1 expression is a marker that effectively distinguishes BC patients from healthy control and predicts worse clinical outcomes in BC. The loss-of-function experiments showed that STIP1 silencing results in inhibition of cell proliferation and migration, inducing cell apoptosis, and S-phase arrest in vitro. Our study also showed that STIP1 downregulation inhibited the JAK2/STAT3 pathway and epithelial-mesenchymal transition process. Rescue experiments demonstrated that the oncogenic effect of STIP1 is partially dependent on mediating JAK2 expression. This study verified that STIP1 is an oncogenic gene that promotes BC progression and serves as a valuable diagnostic and outcome-related marker of BC.

Phospholipase C Delta 3 inhibits apoptosis and promotes proliferation, migration, and invasion of thyroid cancer cells via Hippo pathway.

In recent decades, the incidence of thyroid cancer (TC) has rapidly increased, leading us to explore the complex underlying mechanisms. We identified the gene Phospholipase C Delta 3 (PLCD3) as a potential oncogene in TC by conducting the whole transcriptome sequencing. Our study is to understand the oncogenic role of PLCD3 in TC. We verified the overexpression of PLCD3 in TC from The Cancer Genome Atlas, Gene Expression Omnibus databases, and a locally validated cohort. Clinical correlation analysis showed that PLCD3 expression was related to histological type, T stage, lymph node metastasis (LNM), and disease stage. The high expression of PLCD3 could be a distinguishing factor for TC and its LNM. The biological function was examined using small interfering RNA-transfected TC cell lines. Silenced PLCD3 could inhibit colony formation, migration, and invasion ability and promote apoptosis of TC cell lines. PLCD3 silencing reversed the epithelial-mesenchymal transition but induced the apoptotic progress. Further exploration revealed that PLCD3 might be associated with critical genes of the Hippo pathway. The expressions of RHOA, YAP1/TAZ, and their downstream targets were decreased significantly when PLCD3 was down-regulated. YAP1 overexpression rescued the tumor-suppressive effect caused by PLCD3 silencing. This study demonstrates that PLCD3 is an oncogene that supports tumorigenesis and progression in TC, and PLCD3 may be a potential target gene for TC treatment.

Immortalization up-regulated protein promotes tumorigenesis and inhibits apoptosis of papillary thyroid cancer.

The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up-regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf-like PTC patients with higher IMUP expression had shorter disease-free survival. The biological function of IMUP in PTC cell lines (KTC-1 and TPC-1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis-related molecules were identified by real-time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down-regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC.

Downregulation of Immortalization-Upregulated Protein Suppresses the Progression of Breast Cancer Cell Lines by Regulating Epithelial-Mesenchymal Transition.

INTRODUCTION: Breast cancer (BC) is one of the most prevalent malignancies in women and its incidence has increased steadily over recent years (0.3% per year). However, the mechanism of BC tumorigenesis remains elaborate elucidation. With the aid of RNA sequencing technology, we discovered that immortalization-upregulated protein (IMUP) is overexpressed in BC tissues compared to normal breast tissues. Our study is to understand the role of IMUP in BC. METHODS: We validated the upregulation of IMUP from multiple public databases. By using quantitative real-time polymerase chain reaction (qRT-PCR), we proved that IMUP is overexpressed in BC tissues and cell lines. We performed proliferation, migration, invasion and apoptosis assays to explore the function of IMUP in BC cell lines (MCF-7 and MDA-MB-231). Besides, we investigated the effect of IMUP silencing on epithelial-mesenchymal transition using Western blotting and qRT-PCR. RESULTS AND DISCUSSION: We validated that IMUP expression in BC tissues and cell lines is higher than that in the normal control group. The clinical analysis showed that IMUP is associated with lymph node metastasis and the outcome of neoadjuvant taxol-based therapy. The loss of function assay demonstrated that, with silencing IMUP, the capacities of proliferation, migration, and invasion of BC cell lines were impaired, while the apoptosis rate of cells increased. Meanwhile, the downregulation of IMUP could hinder the procession of epithelial-mesenchymal transition. CONCLUSION: Our study proved that IMUP plays a vital role in BC and acts as a potential target and marker in future therapy.

LOC389641 promotes papillary thyroid cancer progression by regulating the EMT pathway.

Aim: Thyroid cancer (TC) is one of the most common types of endocrine malignancy and poses a significant challenge to human health. The long noncoding RNA 389641 (LOC389641) has been found to be associated with many types of cancer. However, the function of LOC389641 in papillary TC (PTC) remains unknown. Our aim is to explore LOC389641 expression and its role in TC. Materials & methods: The function of LOC389641 was determined by colony formation, migration and invasion assays in PTC. Western blot assays were performed to determine the biomarker of epithelial-mesenchymal transition. Results: In this study, we show that LOC389641 is involved in PTC, which suggests that it may be a target for TC therapies.

Eva-1 homolog A promotes papillary thyroid cancer progression and epithelial-mesenchymal transition via the Hippo signalling pathway.

Recently, the incidence of thyroid cancer is increasing worldwide. Papillary thyroid cancer (PTC) is the most common histological type of thyroid cancer. Whole-transcriptome sequence analysis was performed to further understand the primary molecular mechanisms of the occurrence and progression of PTC. Results showed that Eva-1 homolog A (EVA1A) may be a potential gene for the PTC-associated gene in thyroid cancer. In this work, the role of EVA1A expression in thyroid cancer was investigated. Real-time PCR was performed to detect the expression level of EVA1A in 43 pairs of PTC and four thyroid cancer cell lines. The Cancer Genome Atlas (TCGA) database was used to evaluate the relationship between the expression level of EVA1A and the pathological feature of PTC. The logistic regression analysis of the TCGA data set indicated that the expression of EVA1A was an independent risk factor for tumour, nde and metastasis (TNM) in PTC. This study shows the down-regulation of EVA1A inhibited the colony formation, proliferation, migration and invasion of PTC cell lines. In the protein level, knockdown of EVA1A can regulate the expression of N-cadherin, vimentin, Bcl-xL, Bax, YAP and TAZ. This study indicated that EVA1A was an oncogene associated with PTC.